Molecular markers of human sperm functions
2009, International Journal of Andrology
https://doi.org/10.1111/J.1365-2605.2008.00875.XAbstract
Fertilization is a stepwise process that allows two mature gametes to reach each other, fuse and eventually give rise to a new individual. Despite the tremendous importance of reproduction for species development and maintenance, fertility is decreasing worldwide, with peaks in western countries. It is estimated that about 7% of men experiences problems in conceiving a child because of sperm defects. In such a situation, understanding which are the essential sperm players in each of the steps of the fertilization process is essential for the development of new pharmacological strategies to treat the infertile men, for genetic screening of idiopathic male infertility as well as to produce effective male contraceptive agents. The present review will summarize recent evidence for the identification and characterization of molecular markers of sperm functions with emphasis on post-ejaculatory maturation events and the process of sperm-oocyte interaction.
References (198)
- Adeoya-Osiguwa, S. A. & Fraser, L. R. (1996) Evidence for Ca(2+)-dependent ATPase activity, stimulated by decapaci- tation factor and calmodulin, in mouse sperm. Molecular Reproduction and Development 44, 111-120.
- Aitken, R. J. (2006) Sperm function tests and fertility. International Journal of Andrology 29, 69-75.
- Aitken, R. J. & McLaughlin, E. A.. (2007) Molecular mechanisms of sperm capacitation: progesterone-induced secondary calcium oscillations reflect the attainment of a capacitated state. Society of Reproduction and Fertility Supplement 63, 273-293.
- Aitken, R. J., Buckingham, D. W., Harkiss, D., Paterson, M., Fisher, H. & Irvine, D. S. (1996a) The extragenomic action of progesterone on human spermatozoa is influenced by redox regulated changes in tyrosine phosphorylation during capacitation. Molecular and Cellular Endocrinology 117, 83-93.
- Aitken, R. J., Buckingham, D. W. & Irvine, D. S. (1996b) The extragenomic action of progesterone on human spermato- zoa: evidence for a ubiquitous response that is rapidly down-regulated. Endocrinology 137, 3999-4009.
- Aitken, R. J., Harkiss, D., Knox, W., Paterson, M. & Irvine, D. S. (1998) A novel signal transduction cascade in capacitating human spermatozoa characterised by a redox-regulated, cAMP-mediated induction of tyrosine phosphorylation. Journal of Cell Science 111, 645-656.
- Albarracin, J. L., Fernandez-Novell, J. M., Ballester, J., Rauch, M. C., Quintero-Moreno, A., Pena, A. et al. (2004) Gluco- neogenesis-linked glycogen metabolism is important in the achievement of in vitro capacitation of dog spermatozoa in a medium without glucose. Biology of Reproduction 71, 1437-1445.
- Allgeyer, M., Kirschenhofer, N., Mann, U. & Brucker, C. (2006) Measurement of induced acrosome reactions in human sperm using physiologic stimuli-relevance for the prediction of fertilization outcome. Andrologia 38, 99-105.
- Anderson, M. J. & Dixson, A. F. (2002) Sperm competition: motility and the midpiece in primates. Nature 416, 496.
- Anderson, M. J., Chapman, S. J., Videan, E. N., Evans, E., Fritz, J., Stoinski, T. S., Dixson, A. F. & Gagneux, P. (2007) Functional evidence for differences in sperm competition in humans and chimpanzees. Aerican Journal of Physiology and Anthropology 134, 274-280.
- Aparicio, I. M., Gil, M. C., Garcia-Herreros, M., Pena, F. J. & Garcia-Marin, L. J. (2005) Inhibition of phosphatidylinositol 3-kinase modifies boar sperm motion parameters. Reproduc- tion 129, 283-289.
- Aquila, S., Gentile, M., Middea, E., Catalano, S., Morelli, C., Pezzi, V. & Ando, S. (2005) Leptin secretion by human ejaculated spermatozoa. Journal of Clinical Endocrinology and Metabolism 90, 4753-4761.
- Asquith, K. L., Baleato, R. M., McLaughlin, E. A., Nixon, B. & Aitken, R. J. (2004) Tyrosine phosphorylation activates sur- face chaperones facilitating sperm-zona recognition. Journal of Cell Science 117, 3645-3657.
- Babcock, D. F. (2007) Wrath of the wraiths of CatSper3 and CatSper4. Proceedings of the National Academy of Science of the United States of America 104, 1107-1108.
- Baccetti, B., Collodel, G., Gambera, L., Moretti, E., Serafini, F. & Piomboni, P. (2005) Fluorescence in situ hybridization and molecular studies in infertile men with dysplasia of the fibrous sheath. Fertility and Sterility 84, 123-129.
- Baibakov, B., Gauthier, L., Talbot, P., Rankin, T. L. & Dean, J. (2007) Sperm binding to the zona pellucida is not sufficient to induce acrosome exocytosis. Development 134, 933-943.
- Bajpai, M. & Doncel, G. F. (2003) Involvement of tyrosine kinase and cAMP-dependent kinase cross-talk in the regula- tion of human sperm motility. Reproduction 126, 183-195.
- Bajpai, M., Fiedler, S. E., Huang, Z., Vijayaraghavan, S., Olson, G. E., Livera, G., Conti, M. & Carr, D. W. (2006) AKAP3 selectively binds PDE4A isoforms in bovine spermatozoa. Biology of Reproduction 74, 109-118.
- Baker, M. A., Hetherington, L., Ecroyd, H., Roman, S. D. & Aitken, R. J. (2004) Analysis of the mechanism by which calcium negatively regulates the tyrosine phosphorylation cascade associated with sperm capacitation. Journal of Cell Science 117, 211-222.
- Baker, M. A., Hetherington, L. & Aitken, R. J. (2006) Identifi- cation of SRC as a key PKA-stimulated tyrosine kinase involved in the capacitation-associated hyperactivation of murine spermatozoa. Journal of Cell Science 119, 3182-3192.
- Baker, M. A., Reeves, G., Hetherington, L., Mu ¨ller, J., Baur, I. & Aitken, R. J. (2007) Identification of gene products present in Triton X-100 soluble and insoluble fractions of human spermatozoa lysates using LC-MS ⁄ MS analysis. Proteomics Clinical Applications 1, 524-532.
- Baldi, E., Casano, R., Falsetti, C., Krausz, C., Maggi, M. & Forti, G. (1991) Intracellular calcium accumulation and responsiveness to progesterone in capacitating human spermatozoa. Journal of Andrology 12, 323-330.
- Baldi, E., Falsetti, C., Krausz, C., Gervasi, G., Carloni, V., Casano, R. & Forti, G. (1993) Stimulation of platelet-activat- ing factor synthesis by progesterone and A23187 in human spermatozoa. The Biochemical Journal 292, 209-216.
- Barroso, G., Taylor, S., Morshedi, M., Manzur, F., Gavino, F. & Oehninger, S. (2006) Mitochondrial membrane potential integrity and plasma membrane translocation of phosphati- dylserine as early apoptotic markers: a comparison of two different subpopulations. Fertility and Sterility 85, 149-154.
- Baumber, J. & Meyers, S. A. (2006) Changes in membrane lipid order with capacitation in rhesus macaque (Macaca mulatta) spermatozoa. Journal of Andrology 27, 578-587.
- Baxendale, R. W. & Fraser, L. R. (2003) Evidence for multiple distinctly localized adenylyl cyclase isoforms in mammalian spermatozoa. Molecular and Reproduction Development 66, 181-189.
- Bebington, C., Doherty, F. J. & Fleming, S. D. (2001) The possible biological and reproductive functions of ubiquitin. Human Reproduction Update 7, 102-111.
- Bedu-Addo, K., Lefievre, L., Moseley, F. L., Barratt, C. L. & Publicover, S. J. (2005) Bicarbonate and bovine serum albumin reversibly 'switch' capacitation-induced events in human spermatozoa. Molecular Human Reproduction 11, 683-691.
- Bedu-Addo, K., Barratt, C. L., Kirkman-Brown, J. C. & Publicover, S. J. (2007) Patterns of [Ca2+](i) mobilization and cell response in human spermatozoa exposed to proges- terone. Developmental Biology 302, 324-332.
- Belmonte, S. A., Lopez, C. I., Roggero, C. M., De Blas, G. A., Tomes, C. N. & Mayorga, L. S. (2005) Cholesterol content regulates acrosomal exocytosis by enhancing Rab3A plasma membrane association. Developmental Biology 285, 393-408.
- Bhasin, S.. (2007) Approach to the infertile man. Journal of Clinical Endocrinology and Metabolism 92, 1995-2004. Review.
- Blackmore, P. F. (1993) Rapid non-genomic actions of proges- terone stimulate Ca2+ influx and the acrosome reaction in human sperm. Cell Signalling 5, 531-538.
- Boerke, A., Dieleman, S. J. & Gadella, B. M. (2007) A possible role for sperm RNA in early embryo development. Therioge- nology 68, S147-S155.
- Bonaccorsi, L., Krausz, C., Pecchioli, P., Forti, G. & Baldi, E. (1998) Progesterone-stimulated intracellular calcium increase in human spermatozoa is protein kinase C-independent. Molecular Human Reproduction 4, 259-268.
- Breitbart, H., Rubinstein, S. & Nass-Arden, L. (1985) The role of calcium and Ca2+-ATPase in maintaining motility in ram spermatozoa. Journal of Biological Chemistry 260, 11548-11553.
- Brugnon, F., Van Assche, E., Verheyen, G., Sion, B., Boucher, D., Pouly, J. L., Janny, L., Devroey, P., Liebaers, I. & Van Steirteghem, A. (2006) Study of two markers of apoptosis and meiotic segregation in ejaculated sperm of chromosomal translocation carrier patients. Human Reproduction 21, 685-693.
- Buffone, M. G., Calamera, J. C., Verstraeten, S. V. & Doncel, G. F. (2005) Capacitation-associated protein tyrosine phosphorylation and membrane fluidity changes are impaired in the spermatozoa of asthenozoospermic patients. Reproduction 129, 697-705.
- Burton, K. A. & McKnight, G. S. (2007) PKA, germ cells, and fertility. Physiology 22, 40-46.
- Burton, K. A., Johnson, B. D., Hausken, Z. E., Westenbroek, R. E., Idzerda, R. L., Scheuer, T., Scott, J. D., Catterall, W. A. & McKnight, G. S. (1997) Type II regulatory subunits are not required for the anchoring-dependent modulation of Ca2+ channel activity by cAMP-dependent protein kinase. Proceedings of the National Academy of Sciences of the United States of America 94, 11067-11072.
- Burton, K. A., Treash-Osio, B., Muller, C. H., Dunphy, E. L. & McKnight, G. S. (1999) Deletion of type IIalpha regulatory subunit delocalizes protein kinase A in mouse sperm with- out affecting motility or fertilization. Journal of Biological Chemistry 274, 24131-24136.
- Butler, A., He, X., Gordon, R. E., Wu, H. S., Gatt, S. & Schuchman, E. H. (2002) Reproductive pathology and sperm physiology in acid sphingomyelinase-deficient mice. American Journal of Pathology 161, 1061-1075.
- Butler, A., Gordon, R. E., Gatt, S. & Schuchman, E. H. (2007) Sperm abnormalities in heterozygous acid sphingomyelinase knockout mice reveal a novel approach for the prevention of genetic diseases. American Journal of Pathology 170, 2077-2088.
- Caballero-Campo, P., Chirinos, M., Fan, X. J., Gonzalez-Gonz- alez, M. E., Galicia-Chavarria, M., Larrea, F. & Gerton, G. L. (2006) Biological effects of recombinant human zona pellu- cida proteins on sperm function. Biology of Reproduction 74, 760-768.
- Carrera, A., Moos, J., Ning, X. P., Gerton, G. L., Tesarik, J., Kopf, G. S. & Moss, S. B. (1996) Regulation of protein tyrosine phosphorylation in human sperm by a calcium ⁄ calmodulin-dependent mechanism: identification of A kinase anchor proteins as major substrates for tyrosine phosphory- lation. Developmental Biology 180, 284-296.
- Castilla, J. A., Gil, T., Molina, J., Hortas, M. L., Rodriguez, F., Torres-Munoz, J., Vergara, F. & Herruzo, A. J. (1995) Undetectable expression of genomic progesterone receptor in human spermatozoa. Human Reproduction 10, 1757- 1760.
- Chakravarty, S., Suraj, K. & Gupta, S. K. (2005) Baculovirus- expressed recombinant human zona pellucida glycoprotein- B induces acrosomal exocytosis in capacitated spermatozoa in addition to zona pellucida glycoprotein-C. Molecular Human Reproduction 11, 365-372.
- Chakravarty, S., Kadunganattil, S., Bansal, P., Sharma, R. K. & Gupta, S. K. (2008) Relevance of glycosylation of human zona pellucida glycoproteins for their binding to capacitated human spermatozoa and subsequent induction of acrosomal exocytosis. Molecular Reproduction Development 75, 75-88.
- Chemes, H. E. & Rawe, Y. V. (2003) Sperm pathology: a step beyond descriptive morphology. Origin, characterization and fertility potential of abnormal sperm phenotypes in infertile men. Human Reproduction Update 9, 405-428.
- Chemes, H. E., Brugo, S., Zanchetti, F., Carrere, C. & Lavieri, J. C. (1987) Dysplasia of the fibrous sheath: an ultrastructur- al defect of human spermatozoa associated with sperm immotility and primary sterility. Fertility and Sterility 48, 664-669.
- Chen, Y., Cann, M. J., Litvin, T. N., Iourgenko, V., Sinclair, M. L., Levin, L. R. & Buck, J. (2000) Soluble adenylyl cyclase as an evolutionarily conserved bicarbonate sensor. Science 289, 625-628.
- Clark, G. F. & Dell, A. (2006) Molecular models for murine sperm-egg binding. Journal of Biological Chemistry 281, 13853-13856.
- Conner, S. J., Lefievre, L., Hughes, D. C. & Barratt, C. L. (2005) Cracking the egg: increased complexity in the zona pellucida. Human Reproduction 20, 1148-1152.
- Correia, J. N., Conner, S. J. & Kirkman-Brown, J. C. (2007) Non-genomic steroid actions in human spermatozoa. ''Persistent tickling from a laden environment''. Seminars in Reproductive Medicine 25, 208-219.
- Cotton, L., Gibbs, G. M., Sanchez-Partida, L. G., Morrison, J. R., de Kretser, D. M. & O'Bryan, M. K. (2006) FGFR-1 [corrected] signaling is involved in spermiogenesis and sperm capacitation. Journal of Cell Science 119, 75-84.
- Cross, N. L. (2004) Reorganization of lipid rafts during capaci- tation of human sperm. Biology of Reproduction 71, 1367- 1373.
- Curi, S. M., Ariagno, J. I., Chenlo, P. H., Mendeluk, G. R., Pugliese, M. N., Sardi Segovia, L. M., Repetto, H. E. & Blanco, A. M. (2003) Asthenozoospermia: analysis of a large population. Archives of Andrology 49, 343-349.
- Damjanov, I., Solter, D. & Knowles, B. B. (1993) Functional epidermal growth factor receptor localizes to the postacroso- mal region of human spermatozoa. Biochemical and Biophys- ical Research Communication 190, 901-906.
- Darszon, A., Nishigaki, T., Wood, C., Trevino, C. L., Felix, R. & Beltran, C. (2005) Calcium channels and Ca2+ fluctua- tions in sperm physiology. International Review of Cytology 243, 79-172.
- DasGupta, S., Mills, C. L. & Fraser, L. R. (1993) Ca(2+)- related changes in the capacitation state of human sperma- tozoa assessed by a chlortetracycline fluorescence assay. Journal of Reproduction and Fertility 99, 135-143.
- De Blas, G., Michaut, M., Trevino, C. L., Tomes, C. N., Yunes, R., Darszon, A. & Mayorga, L. S. (2002) The intraacrosomal calcium pool plays a direct role in acrosomal exocytosis. Journal of Biological Chemistry 277, 49326-49331.
- De Jonge, C. (2005) Biological basis for human capacitation. Human Reproduction Update 11, 205-214.
- De Lamirande, E. & Gagnon, C. (2002) The extracellular signal-regulated kinase (ERK) pathway is involved in human sperm function and modulated by the superoxide anion. Molecular Human Reproduction 8, 124-135.
- Diez-Sanchez, C., Ruiz-Pesini, E., Montoya, J., Perez-Martos, A., Enriquez, J. A. & Lopez-Perez, M. J. (2003) Mitochon- dria from ejaculated human spermatozoa do not synthesize proteins. FEBS Letter 553, 205-208.
- Du, J., Tao, J., Kleinhans, F. W., Mazur, P. & Critser, J. K. (1994) Water volume and osmotic behaviour of mouse spermatozoa determined by electron paramagnetic reso- nance. Journal of Reproduction and Fertility 101, 37-42.
- Ellerman, D. A., Cohen, D. J., Da Ros, V. G., Morgenfeld, M. M., Busso, D. & Cuasnicu, P. S. (2006) Sperm protein ''DE'' mediates gamete fusion through an evolutionarily conserved site of the CRISP family. Developmental Biology 297, 228-237.
- Erenpreiss, J., Spano, M., Erenpreisa, J., Bungum, M. & Giwercman, A. (2006) Sperm chromatin structure and male fertility: biological and clinical aspects. Asian Journal of An- drology 8, 11-29.
- Esposito, G., Jaiswal, B. S., Xie, F., Krajnc-Franken, M. A., Robben, T. J., Strik, A. M. et al. (2004) Mice deficient for soluble adenylyl cyclase are infertile because of a severe sperm-motility defect. Proceedings of the National Academy of Sciences of the United States of America 101, 2993-2998.
- Etkovitz, N., Rubinstein, S., Daniel, L. & Breitbart, H. (2007) Role of PI3-kinase and PI4-kinase in actin polymerization during bovine sperm capacitation. Biology of Reproduction 77, 263-273.
- Falsetti, C., Baldi, E., Krausz, C., Casano, R., Failli, P. & Forti, G. (1993) Decreased responsiveness to progesterone of spermatozoa in oligozoospermic patients. Journal of Andrology 14, 17-22.
- Felix, R. (2005) Molecular physiology and pathology of Ca2+- conducting channels in the plasma membrane of mamma- lian sperm. Reproduction 129, 251-262.
- Ficarro, S., Chertihin, O., Westbrook, V. A., White, F., Jayes, F., Kalab, P. et al. (2003) Phosphoproteome analysis of capacitated human sperm. Evidence of tyrosine phosphorylation of a kinase-anchoring protein 3 and valosin-containing protein ⁄ p97 during capacitation. Journal of Biological Chemistry 278, 11579-11589.
- Flesch, F. M., Brouwers, J. F., Nievelstein, P. F., Verkleij, A. J., van Golde, L. M., Colenbrander, B. & Gadella, B. M. (2001) Bicarbonate stimulated phospholipid scrambling induces cholesterol redistribution and enables cholesterol depletion in the sperm plasma membrane. Journal of Cell Science 114, 3543-3555.
- Ford, W. C. (2006) Glycolysis and sperm motility: does a spoonful of sugar help the flagellum go round? Human Reproduciton Update 12, 269-274.
- Francavilla, F., Romano, R., Gabriele, A. R., Santucci, R., Marrone, V. & Francavilla, S. (1994) Impaired hamster egg penetration by human sperm from ejaculates with low acrosin activity but otherwise normal. Fertility and Sterility 61, 735-740.
- Francavilla, S., Pelliccione, F., Cordeschi, G., Necozione, S., Santucci, R., Bocchio, M., Mihalca, R., Ciociola, F. & Fran- cavilla, F. (2006) Utrastructural analysis of asthenozoosper- mic ejaculates in the era of assisted procreation. Fertility and Sterility 85, 940-946.
- Fraser, L. R. & Quinn, P. J. (1981) A glycolytic product is obligatory for initiation of the sperm acrosome reaction and whiplash motility required for fertilization in the mouse. Journal of Reproduction and Fertility 61, 25-35.
- Fraser, L. R., Adeoya-Osiguwa, S. A., Baxendale, R. W. & Gibbons, R. (2006) Regulation of mammalian sperm capacitation by endogenous molecules. Frontiers in Bioscience 11, 1636-1645.
- Frederick, J. L., Francis, M. M., Macaso, T. M., Lobo, R. A., Sauer, M. V. & Paulson, R. J. (1991) Preovulatory follicular fluid steroid levels in stimulated and unstimulated cycles triggered with human chorionic gonadotropin. Fertility and Sterility 55, 44-47.
- Furuya, S., Endo, Y., Oba, M., Suzuki, S. & Nozawa, S. (1993) Effect of epidermal growth factor on human sperm capacita- tion. Fertility and Sterility 60, 905-910.
- Gadella, B. M. & Harrison, R. A. (2002) Capacitation induces cyclic adenosine 3',5'-monophosphate-dependent, but apoptosis-unrelated, exposure of aminophospholipids at the apical head plasma membrane of boar sperm cells. Biology of Reproduction 67, 340-350.
- Garcia, M. A. & Meizel, S. (1999) Progesterone-mediated cal- cium influx and acrosome reaction of human spermatozoa: pharmacological investigation of T-type calcium channels. Biology of Reproduction 60, 102-109.
- Georgiou, I., Syrrou, M., Pardalidis, N., Karakitsios, K., Mantz- avinos, T., Giotitsas, N. et al. (2006) Genetic and epigenetic risks of intracytoplasmic sperm injection method. Asian Journal of Andrology 8, 643-673.
- Gur, Y. & Breitbart, H. (2006) Mammalian sperm translate nuclear-encoded proteins by mitochondrial-type ribosomes. Genes and Development 20, 411-416.
- Hayasaka, S., Terada, Y., Inoue, N., Okabe, M., Yaegashi, N. & Okamura, K. (2007) Positive expression of the immunoglob- ulin superfamily protein IZUMO on human sperm of severe male infertile patients. Fertility and Sterility 88, 214-216.
- Hess, K. C., Jones, B. H., Marquez, B., Chen, Y., Ord, T. S., Kamenetsky, M. et al. (2005) The ''soluble'' adenylyl cyclase in sperm mediates multiple signaling events required for fertilization. Developmental Cell 9, 249-259.
- Ho, H. C.. & Suarez, S. S. (2001) Hyperactivation of mamma- lian spermatozoa: function and regulation. Reproduction 122, 519-526.
- Ho, H. C. & Suarez, S. S. (2003) Characterization of the intracellular calcium store at the base of the spermflagellum that regulates hyperactivated motility. Biology of Reproduc- tion 68, 1590-1596.
- Hochstrasser, M. (1996) Ubiquitin-dependent protein degradation. Annual Review of Genetic 30, 405-439.
- Holz, G. G., Chepurny, O. G. & Schwede, F. (2008) Epac-selective cAMP analogs: new tools with which to evaluate the signal transduction properties of cAMP-regu- lated guanine nucleotide exchange factors. Cell Signalling 20, 10-20.
- Huang, Z., Somanath, P. R., Chakrabarti, R., Eddy, E. M. & Vijayaraghavan, S. (2005) Changes in intracellular distribu- tion and activity of protein phosphatase PP1gamma2 and its regulating proteins in spermatozoa lacking AKAP4. Biology of Reproduction 72, 384-392.
- Inaba, K. (2003) Molecular architecture of the sperm flagella: molecules for motility and signaling. Zoological Science 20, 1043-1056.
- Inoue, N., Ikawa, M., Isotani, A. & Okabe, M. (2005) The immunoglobulin superfamily protein Izumo is required for sperm to fuse with eggs. Nature 434, 234-238.
- Isobe, T., Minoura, H., Tanaka, K., Shibahara, T., Hayashi, N. & Toyoda, N. (2002) The effect of RANTES on human sperm chemotaxis. Human Reproduction 17, 1441-1446.
- Jacob, A., Hurley, I., Mandel, F. S., Hershlag, A., Cooper, G. W. & Benoff, S. (1998) Human sperm non-nuclear proges- terone receptor expression is a novel marker for fertilization outcome. Molecular Human Reproduction 4, 533-542.
- Jaiswal, B. S. & Conti, M. (2001) Identification and functional analysis of splice variants of the germ cell soluble adenylyl cyclase. Journal of Biological Chemistry 276, 31698-31708.
- Jha, K. N., Salicioni, A. M., Arcelay, E., Chertihin, O., Kumari, S., Herr, J. C. & Visconti, P. E. (2006) Evidence for the involvement of proline-directed serine ⁄ threonine phosphor- ylation in sperm capacitation. Molecular Human Reproduc- tion 12, 781-789.
- Jimenez-Gonzalez, C., Michelangeli, F., Harper, C. V., Barratt, C. L. & Publicover, S. J. (2006) Calcium signalling in human spermatozoa: a specialized 'toolkit' of channels, transporters and stores. Human Reproduction Update 12, 253-267.
- Jungnickel, M. K., Marrero, H., Birnbaumer, L., Lemos, J. R. & Florman, H. M. (2001) Trp2 regulates entry of Ca2+ into mouse sperm triggered by egg ZP3. Nature Cell Biology 3, 499-502.
- Jungnickel, M. K., Sutton, K. A., Wang, Y. & Florman, H. M. (2007) Phosphoinositide-dependent pathways in mouse sperm are regulated by egg ZP3 and drive the acrosome reaction. Developmental Biology 304, 116-126.
- Kaji, K., Oda, S., Miyazaki, S. & Kudo, A. (2002) Infertility of CD9-deficient mouse eggs is reversed by mouse CD9, human CD9, or mouse CD81; polyadenylated mRNA injection developed for molecular analysis of sperm-egg fusion. Developmental Biology 247, 327-334.
- Kalab, P., Peknicova, J., Geussova, G. & Moos, J. (1998) Regulation of protein tyrosine phosphorylation in boar sperm through a cAMP-dependent pathway. Molecular Reproduction and Development 51, 304-314.
- Kholkute, S. D., Meherji, P. & Puri, C. P. (1992) Capacitation and the acrosome reaction in sperm from men with various semen profiles monitored by a chlortetracycline fluorescence assay. International Journal of Andrology 15, 43-53.
- Krausz, C., Bonaccorsi, L., Luconi, M., Fuzzi, B., Criscuoli, L., Pellegrini, S., Forti, G. & Baldi, E. (1995) Intracellular calcium increase and acrosome reaction in response to progesterone in human spermatozoa are correlated with in-vitro fertilization. Human Reproduction 10, 120-124.
- Krausz, C., Bonaccorsi, L., Maggio, P., Luconi, M., Criscuoli, L., Fuzzi, B., Pellegrini, S., Forti, G. & Baldi, E. (1996) Two functional assays of sperm responsiveness to progesterone and their predictive values in in-vitro fertilization. Human Reproduction 11, 1661-1667.
- Krisfalusi, M., Miki, K., Magyar, P. L. & O'Brien, D. A. (2006) Multiple glycolytic enzymes are tightly bound to the fibrous sheath of mouse spermatozoa. Biology of Reproduction 75, 270-278.
- Kumar, V., Rangaraj, N. & Shivaji, S. (2006) Activity of pyruvate dehydrogenase A (PDHA) in hamster spermatozoa correlates positively with hyperactivation and is associated with sperm capacitation. Biology of Reproduction 75, 767-777.
- Lalancette, C., Faure, R. L. & Leclerc, P. (2006) Identification of the proteins present in the bull sperm cytosolic fraction enriched in tyrosine kinase activity: a proteomic approach. Proteomics 6, 4523-4540.
- Leclerc, P., de Lamirande, E. & Gagnon, C. (1996) Cyclic adenosine 3',5'monophosphate-dependent regulation of protein tyrosine phosphorylation in relation to human sperm capacitation and motility. Biology of Reproduction 55, 684-692.
- Lefievre, L., Conner, S. J., Salpekar, A., Olufowobi, O., Ashton, P., Pavlovic, B. et al. (2004) Four zona pellucida glycopro- teins are expressed in the human. Human Reproduction 19, 1580-1586.
- Li, Z., Wang, L., Cai, J. & Huang, H. (2006) Correlation of sperm DNA damage with IVF and ICSI outcomes: a system- atic review and meta-analysis. Journal of Assisted Reproduc- tion and Genetic 23, 367-376.
- Li, H. G., Ding, X. F., Liao, A. H., Kong, X. B. & Xiong, C. L. (2007) Expression of CatSper family transcripts in the mouse testis during post-natal development and human ejaculated spermatozoa: relationship to sperm motility. Molecular Human Reproduction 13, 299- 306. Liguori, L., de Lamirande, E., Minelli, A. & Gagnon, C. (2005) Various protein kinases regulate human sperm acrosome reaction and the associated phosphorylation of Tyr residues and of the Thr-Glu-Tyr motif. Molecular Human Reproduc- tion 11, 211-221.
- Liu, D. Y., Clarke, G. N. & Baker, H. W. (2006) Tyrosine phosphorylation on capacitated human sperm tail detected by immunofluorescence correlates strongly with sperm-zona pellucida (ZP) binding but not with the ZP-induced acrosome reaction. Human Reproduction 21, 1002-1008.
- Livera, G., Xie, F., Garcia, M. A., Jaiswal, B., Chen, J., Law, E., Storm, D. R. & Conti, M. (2005) Inactivation of the mouse adenylyl cyclase 3 gene disrupts male fertility and spermato- zoon function. Molecular Endocrinology 19, 1277-1290.
- Lopes, S., Sun, J. G., Jurisicova, A., Meriano, J. & Casper, R. F. (1998) Sperm deoxyribonucleic acid fragmentation is increased in poor-quality semen samples and correlates with failed fertilization in intracytoplasmic sperm injection. Fertility and Sterility 69, 528-532.
- Luconi, M., Bonaccorsi, L., Krausz, C., Gervasi, G., Forti, G. & Baldi, E. (1995) Stimulation of protein tyrosine phosphory- lation by platelet-activating factor and progesterone in human spermatozoa. Molecular and Cellular Endocrinology 108, 35-42.
- Luconi, M., Krausz, C., Forti, G. & Baldi, E. (1996) Extracellu- lar calcium negatively modulates tyrosine phosphorylation and tyrosine kinase activity during capacitation of human spermatozoa. Biology of Reproduction 55, 207-216.
- Luconi, M., Barni, T., Vannelli, G. B., Krausz, C., Marra, F., Benedetti, P. A. et al. (1998a) Extracellular signal-regulated kinases modulate capacitation of human spermatozoa. Biology of Reproduction 58, 1476-1489.
- Luconi, M., Bonaccorsi, L., Maggi, M., Pecchioli, P., Krausz, C., Forti, G. & Baldi, E. (1998b) Identification and charac- terization of functional nongenomic progesterone receptors on human sperm membrane. Journal of Clinical Endocrinol- ogy and Metabolism 83, 877-885.
- Luconi, M., Krausz, C., Barni, T., Vannelli, G. B., Forti, G. & Baldi, E. (1998c) Progesterone stimulates p42 extracellular signal-regulated kinase (p42erk) in human spermatozoa. Molecular Human Reproduction 4, 251-258.
- Luconi, M., Marra, F., Gandini, L., Filimberti, E., Lenzi, A., Forti, G. & Baldi, E. (2001) Phosphatidylinositol 3-kinase inhibition enhances human sperm motility. Human Repro- duction 16, 1931-1937.
- Luconi, M., Carloni, V., Marra, F., Ferruzzi, P., Forti, G. & Baldi, E. (2004) Increased phosphorylation of AKAP by inhibition of phosphatidylinositol 3-kinase enhances human sperm motility through tail recruitment of protein kinase A. Journal of Cell Science 117, 1235-1246.
- Luconi, M., Porazzi, I., Ferruzzi, P., Marchiani, S., Forti, G. & Baldi, E. (2005) Tyrosine phosphorylation of the a kinase anchoring protein 3 (AKAP3) and soluble adenylate cyclase are involved in the increase of human sperm motility by bicarbonate. Biology of Reproduction 72, 22-32.
- Luconi, M., Forti, G. & Baldi, E. (2006) Pathophysiology of sperm motility. Frontiers in Bioscience 11, 1433- 1447.
- Marchiani, S., Tamburrino, L., Maoggi, A., Vannelli, G. B., Forti, G., Baldi, E. & Muratori, M. (2007) Characterization of M540 bodies in human semen: evidence that they are apoptotic bodies. Molecular Human Reproduction 13, 621-631.
- Marquez, B., Ignotz, G. & Suarez, S. S. (2007) Contributions of extracellular and intracellular Ca2+ to regulation of sperm motility: release of intracellular stores can hyper- activate CatSper1 and CatSper2 null sperm. Developmental Biology 303, 214-221.
- Martin, G., Sabido, O., Durand, P. & Levy, R. (2005) Phos- phatidylserine externalization in human sperm induced by calcium ionophore A23187: relationship with apoptosis, membrane scrambling and the acrosome reaction. Human Reproduction 20, 3459-3468.
- Miki, K., Qu, W., Goulding, E. H., Willis, W. D., Bunch, D. O., Strader, L. F., Perreault, S. D., Eddy, E. M. & O'Brien, D. A. (2004) Glyceraldehyde 3-phosphate dehydrogenase-S, a sperm-specific glycolytic enzyme, is required for sperm motility and male fertility. Proceedings of the National Academy of Sciences of the United States of America 101, 16501-16506.
- Minelli, A., Liguori, L., Bellazza, I., Mannucci, R., Johansson, B. & B. B. (2004) Involvement of A1 adenosine receptors in the acquisition of fertilizing capacity. Journal of Andrology 25, 286-292.
- Mitchell, L. A., Nixon, B. & Aitken, R. J. (2007) Analysis of chaperone proteins associated with human spermatozoa during capacitation. Molecular Human Reproduction 13, 605-613.
- Mitra, K., Rangaraj, N. & Shivaji, S. (2005) Novelty of the pyruvate metabolic enzyme dihydrolipoamide dehydrogenase in spermatozoa: correlation of its localization, tyrosine phos- phorylation, and activity during sperm capacitation. Journal of Biological Chemistry 280, 25743-25753.
- Moseley, F. L., Jha, K. N., Bjorndahl, L., Brewis, I. A., Publicover, S. J., Barratt, C. L. & Lefievre, L. (2005) Protein tyrosine phosphorylation, hyperactivation and progesterone- induced acrosome reaction are enhanced in IVF media: an effect that is not associated with an increase in protein kinase A activation. Molecular Human Reproduction 11, 523-529.
- Moss, S. B. & Gerton, G. L. (2001) A-kinase anchor proteins in endocrine system and reproduction. Trends in Endocrinol- ogy and Metabolism 12, 434-440.
- Muciaccia, B., Padula, F., Vicini, E., Gandini, L., Lenzi, A. & Stefanini, M. (2005) Beta-chemokine receptors 5 and 3 are expressed on the head region of human spermatozoon. FASEB Journal 19, 2048-2050.
- Muratori, M., Porazzi, I., Luconi, M., Marchiani, S., Forti, G. & Baldi, E. (2004) AnnexinV binding and merocyanine staining fail to detect human sperm capacitation. Journal of Andrology 25, 797-810.
- Muratori, M., Marchiani, S., Forti, G. & Baldi, E. (2005) Sperm ubiquitination positively correlates to normal morphology in human semen. Human Reproduction 20, 1035-1043.
- Muratori, M., Marchiani, S., Maggi, M., Forti, G. & Baldi, E. (2006) Origin and biological significance of DNA fragmenta- tion in human spermatozoa. Frontiers in Bioscience 11, 1491-1499.
- Muratori, M., Marchiani, S., Tamburrino, L., Tocci, V., Forti, G. & Baldi, E. (2008) Nuclear staining identifies two popula- tions of human sperm with different DNA fragmentation extent and relationship with semen parameters. Human Reproduction, in press.
- Naaby-Hansen, S., Mandal, A., Wolkowicz, M. J., Sen, B., Westbrook, V. A., Shetty, J. et al. (2002) CABYR, a novel calcium-binding tyrosine phosphorylation-regulated fibrous sheath protein involved in capacitation. Developmental Biol- ogy 242, 236-254.
- Narisawa, S., Hecht, N. B., Goldberg, E., Boatright, K. M., Reed, J. C. & Millan, J. L. (2002) Testis-specific cytochrome c-null mice produce functional sperm but undergo early testicular atrophy. Molecular Cell Biology 22, 5554-5562.
- Nauc, V., De Lamirande, E., Leclerc, P. & Gagnon, C. (2004) Inhibitors of phosphoinositide 3-kinase, LY294002 and wortmannin, affect sperm capacitation and associated phosphorylation of proteins differently: Ca2+-dependent divergences. Journal of Andrology 25, 573-585.
- Naz, R. K. & Ahmad, K. (1992) Presence of expression prod- ucts of c-erbB-1 and c-erbB-2 ⁄ HER2 genes on mammalian sperm cell, and effects of their regulation on fertilization. Journal of Reproductive Immunology 21, 223-239.
- Nikpoor, P., Mowla, S. J., Movahedin, M., Ziaee, S. A. & Tiraihi, T. (2004) CatSper gene expression in postnatal development of mouse testis and in subfertile men with deficient sperm motility. Human Reproduction 19, 124-128.
- Nixon, B., MacIntyre, D. A., Mitchell, L. A., O'Bryan, M. K. & Aitken, R. J. (2006) The identification of mouse sperm surface-associated proteins and characterization of their abil- ity to act as decapacitation factors. Biology of Reproduction 74, 275-287.
- Nolan, M. A., Babcock, D. F., Wennemuth, G., Brown, W., Burton, K. A. & McKnight, G. S. (2004) Sperm-specific protein kinase A catalytic subunit Calpha2 orchestrates cAMP signaling for male fertility. Proceedings of the National Academy of Sciences of the United States of America 101, 13483-13488.
- O'Brien, J. & Zini, A. (2005) Sperm DNA integrity and male infertility. Urology 65, 16-22.
- O'Flaherty, C., de Lamirande, E. & Gagnon, C. (2005) Reactive oxygen species and protein kinases modulate the level of phospho-MEK-like proteins during human sperm capacita- tion. Biology of Reproduction 73, 94-105.
- O'Toole, C. M., Arnoult, C., Darszon, A., Steinhardt, R. A. & Florman, H. M. (2000) Ca(2+) entry through store-operated channels in mouse sperm is initiated by egg ZP3 and drives the acrosome reaction. Molecular Biology of the Cell 11, 1571-1584.
- Oehninger, S., Sueldo, C., Lanzendorf, S., Mahony, M., Burkman, L. J., Alexander, N. J. & Hodgen, G. D. (1994) A sequential analysis of the effect of progesterone on specific sperm functions crucial to fertilization in vitro in infertile patients. Human Reproduction 9, 1322-1327.
- Ozanon, C., Chouteau, J. & Sutovsky, P. (2005) Clinical adaptation of the sperm ubuquitin tag immunoassay (SUTI): relationship of sperm ubiquitylation with sperm quality in gradient-purified semen samples from 93 men from a general infertility clinic population. Human Reproduction 20, 2271-2278.
- Palermo, G., Joris, H., Devroey, P. & Van Steirteghem, A. C. (1992) Pregnancies after intracytoplasmic injection of single spermatozoon into an oocyte. Lancet 340, 17-18.
- Perreault, S. D. & Rogers, B. J. (1982) Capacitation pattern of human spermatozoa. Fertility and Sterility 38, 258-260.
- Platts, A. E., Dix, D. J., Chemes, H. E., Thompson, K. E., Goodrich, R., Rockett, J. C. et al. (2007) Success and Failure in Human Spermatogenesis as Revealed by Teratozoosper- mic RNAs. Human Molecular Genetic 16, 763-773.
- Publicover, S., Harper, C. V. & Barratt, C. (2007) [Ca2+]i signalling in sperm-making the most of what you've got. Nature Cell Biology 9, 235-242.
- Qi, H., Moran, M. M., Navarro, B., Chong, J. A., Krapivin- sky, G., Krapivinsky, L., Kirichok, Y., Ramsey, I. S., Quill, T. A. & Clapham, D. E. (2007) All four CatSper ion channel proteins are required for male fertility and sperm cell hyperactivated motility. Proceedings of the National Academy Sciences of the United States of America 104, 1219-1223.
- Quill, T. A., Sugden, S. A., Rossi, . K. L., Doolittle, L. K., Hammer, R. E. & Garbers, D. L. (2003) Hyperactivated sperm motility driven by CatSper2 is required for fertiliza- tion. Proceedings of the National Academy of Sciences of the United States of America 100, 14869-14874.
- Rassoulzadegan, M., Grandjean, V., Gounon, P., Vincent, S., Gillot, I. & Cuzin, F. (2006) RNA-mediated non-mendelian inheritance of an epigenetic change in the mouse. Nature 441, 469-474.
- Ren, D., Navarro, B., Perez, G., Jackson, A. C., Hsu, S., Shi, Q., Tilly, J. L. & Clapham, D. E. (2001) A sperm ion channel required for sperm motility and male fertility. Nature 413, 603-609.
- Rodeheffer, C. & Shur, B. D. (2004) Sperm from beta1,4-galac- tosyltransferase I-null mice exhibit precocious capacitation. Development 131, 491-501.
- Roldan, E. R., Murase, T. & Shi, Q. X. (1994) Exocytosis in spermatozoa in response to progesterone and zona pellucida. Science 266, 1578-1581.
- Roy, A., Lin, Y. N., Agno, J. E., DeMayo, F. J. & Matzuk, M. M. (2007) Absence of tektin 4 causes asthenozoosper- mia and subfertility in male mice. FASEB Journal 21, 1013-1025.
- Sabeur, K., Edwards, D. P. & Meizel, S. (1996) Human sperm plasma membrane progesterone receptor(s) and the acro- some reaction. Biology of Reproduction 54, 993-1001.
- Shadan, S., James, P. S., Howes, E. A. & Jones, R. (2004) Cholesterol efflux alters lipid raft stability and distribution during capacitation of boar spermatozoa. Biology of Reproduction 71, 253-265.
- Shi, Q. X., Chen, W. Y., Yuan, Y. Y., Mao, L. Z., Yu, S. Q., Chen, A. J., Ni, Y. & Roldan, E. R. (2005) Progesterone primes zona pellucida-induced activation of phospholipase A2 during acrosomal exocytosis in guinea pig spermatozoa. Journal of Cellular Physiology 205, 344-354.
- Shivaji, S. & Jagannadham, M. V. (1992) Steroid-induced perturbations of membranes and its relevance to sperm acro- some reaction. Biochimica et Biophysica Acta 1108, 99-109.
- Skalhegg, B. S., Huang, Y., Su, T., Idzerda, R. L., McKnight, G. S. & Burton, K. A. (2002) Mutation of the Calpha subunit of PKA leads to growth retardation and sperm dysfunction. Molecular Endocrinology 16, 630-639.
- Spehr, M., Gisselmann, G., Poplawski, A., Riffell, J. A., Wetzel, C. H., Zimmer, R. K. & Hatt, H. (2003) Identification of a testicular odorant receptor mediating human sperm chemo- taxis. Science 299, 2054-2058.
- Sutovsky, P.. (2003) Ubiquitin-dependent proteolysis in mammalian spermatogenesis, fertilization, and sperm quality control: killing three birds with one stone. Microscopy Research and Technique 61, 88-102. Review.
- Sutovsky, P., Moreno, R., Ramalho-Santos, J., Dominko, T., Thompson, W. E. & Schatten, G. (2001a) A putative, ubiquitin-dependent mechanism for the recognition and elimination of defective spermatozoa in the mammalian epididymis. Journal Cell Science 114, 1665-1675.
- Sutovsky, P., Terada, Y. & Schatten, G. (2001b) Ubiquitin- based sperm assay for the diagnosis of male factor infertility. Human Reproduction 16, 250-258.
- Sutovsky, P., Hauser, R. & Sutovsky, M. (2004) Increased levels of sperm ubiquitin correlate with semen quality in men from an andrology laboratory clinic population. Human Reproduction 19, 628-638.
- Tanaka, H., Iguchi, N., Toyama, Y., Kitamura, K., Takahashi, T., Kaseda, K., Maekawa, M. & Nishimune, Y. (2004) Mice deficient in the axonemal protein Tektin-t exhibit male infertility and immotile-cilium syndrome due to impaired inner arm dynein function. Molecular and Cellular Biology 24, 7958-7964.
- Taylor, S. L., Weng, S. L., Fox, P., Duran, E. H., Morshedi, M. S., Oehninger, S. & Beebe, S. J. (2004) Somatic cell apopto- sis markers and pathways in human ejaculated sperm: potential utility as indicators of sperm quality. Molecular Human Reproduction 10, 825-834.
- Tesarik, J. & Mendoza, C. (1992) Defective function of a nongenomic progesterone receptor as a sole sperm anomaly in infertile patients. Fertility and Sterility 58, 793-797.
- Tesarik, J., Moos, J. & Mendoza, C. (1993) Stimulation of protein tyrosine phosphorylation by a progesterone receptor on the cell surface of human sperm. Endocrinology 133, 328-335.
- Tomes, C. N., McMaster, C. R. & Saling, P. M. (1996) Activation of mouse sperm phosphatidylinositol-4,5 bisphos- phate-phospholipase C by zona pellucida is modulated by tyrosine phosphorylation. Molecular Reproduction and Development 43, 196-204.
- Travis, A. J. & Kopf, G. S. (2002) The role of cholesterol efflux in regulating the fertilization potential of mammalian spermatozoa. Journal of Clinical Investigation 110, 731-736.
- Turner, R. M. (2006) Moving to the beat: a review of mamma- lian sperm motility regulation. Reproduction Fertility and Development 18, 25-38.
- Turner, R. M., Eriksson, R. L., Gerton, G. L. & Moss, S. B. (1999) Relationship between sperm motility and the processing and tyrosine phosphorylation of two human sperm fibrous sheath proteins, pro-hAKAP82 and hAKAP82. Molecular Human Reproduction 5, 816-824.
- Turner, R. M., Musse, M. P., Mandal, A., Klotz, K., Jayes, F. C., Herr, J. C., Gerton, G. L., Moss, S. B. & Chemes, H. E. (2001) Molecular genetic analysis of two human sperm fibrous sheath proteins, AKAP4 and AKAP3, in men with dysplasia of the fibrous sheath. Journal of Andrology 22, 302-315.
- Twigg, J. P., Irvine, D. S. & Aitken, R. J. (1998) Oxidative damage to DNA in human spermatozoa does not preclude pronucleus formation at intracytoplasmic sperm injection. Human Reproduction 13, 1864-1871.
- Urner, F. & Sakkas, D. (1996) Glucose participates in sperm-oocyte fusion in the mouse. Biology of Reproduction 55, 917-922.
- Varum, S., Bento, C., Sousa, A. P., Gomes-Santos, C. S., Henriques, P., Almeida-Santos, T., Teodosio, C., Paiva, A. & Ramalho-Santos, J. (2007) Characterization of human sperm populations using conventional parameters, surface ubiquiti- nation, and apoptotic markers. Fertility and Sterility 87, 572-583.
- Vernon, G. G., Neesen, J. & Woolley, D. M. (2005) Further studies on knockout mice lacking a functional dynein heavy chain (MDHC7). 1. Evidence for a structural deficit in the axoneme. Cell Motility and the Cytoskeleton 61, 65-73.
- Verpoest, W. & Tournaye, H. (2006) ICSI: hype or hazard? Human Fertility 9, 81-92.
- Vijayaraghavan, S., Goueli, S. A., Davey, M. P. & Carr, D. W. (1997) Protein kinase A-anchoring inhibitor peptides arrest mammalian sperm motility. Journal of Biological Chemistry 272, 4747-4752.
- Visconti, P. E., Bailey, J. L., Moore, G. D., Pan, D., Olds- Clarke, P. & Kopf, G. S. (1995a) Capacitation of mouse spermatozoa. I. Correlation between the capacitation state and protein tyrosine phosphorylation. Development 121, 1129-1137.
- Visconti, P. E., Moore, G. D., Bailey, J. L., Leclerc, P., Connors, S. A., Pan, D., Olds-Clarke, P. & Kopf, G. S. (1995b) Capacitation of mouse spermatozoa. II. Protein tyrosine phosphorylation and capacitation are regulated by a cAMP-dependent pathway. Development 121, 1139-1150.
- de Vries, K. J., Wiedmer, T., Sims, P. J. & Gadella, B. M. (2003) Caspase-independent exposure of aminophospho- lipids and tyrosine phosphorylation in bicarbonate respon- sive human sperm cells. Biology of Reproduction 68, 2122-2134.
- Wade, M. A., Roman, S. D., Jones, R. C. & Aitken, R. J. (2003) Adenylyl cyclase isoforms in rat testis and spermatozoa from the cauda epididymis. Cell and Tissue Research 314, 411-419.
- Walensky, L. D. & Snyder, S. H. (1995) Inositol 1,4,5-trisphos- phate receptors selectively localized to the acrosomes of mammalian sperm. Journal of Cell Biology 130, 857-869.
- Wang, L., Beserra, C. & Garbers, D. L. (2004) A novel amino- phospholipid transporter exclusively expressed in spermato- zoa is required for membrane lipid asymmetry and normal fertilization. Developmental Biology 267, 203-215.
- Ward, C. R. & Kopf, G. S. (1993) Molecular events mediating sperm activation. Developmental Biology 158, 9-34.
- World Health Organization (1999) WHO Laboratory Manual for the Examination of Human Semen and Sperm-Cervical Mucus Interactions. 4th edn. Cambridge University Press, Cambridge, UK.
- Wu, C., Stojanov, T., Chami, O., Ishii, S., Shimizu, T., Li, A. & O'Neill, C. (2001) Evidence for the autocrine induction of capacitation of mammalian spermatozoa. Journal of Biologi- cal Chemistry 276, 26962-26968.
- Xie, F., Garcia, M. A., Carlson, A. E., Schuh, S. M., Babcock, D. F., Jaiswal, B. S., Gossen, J. A., Esposito, G., van Duin, M. & Conti, M. (2006) Soluble adenylyl cyclase (sAC) is indispensable for sperm function and fertilization. Develop- mental Biology 296, 353-362.
- Yatsenko, A. N., Roy, A., Chen, R., Ma, L., Murthy, L. J., Yan, W., Lamb, D. J. & Matzuk, M. M. (2006) Non-invasive genetic diagnosis of male infertility using spermatozoal RNA: KLHL10 mutations in oligozoospermic patients impair homodimerization. Human Molecular Genetic 15, 3411-3419.
- Yunes, R., Doncel, G. F. & Acosta, A. A. (2003) Incidence of sperm-tail tyrosine phosphorylation and hyperactivated motility in normozoospermic and asthenozoospermic human sperm samples. Biocell 27, 29-36.
- Zahn, A., Furlong, L. I., Biancotti, J. C., Ghiringhelli, P. D., Marijn-Briggiler, C. I. & Vazquez-Levin, M. H. (2002) Evaluation of the proacrosin ⁄ acrosin system and its mecha- nism of activation in human sperm extracts. Journal of Reproductive Immunology 54, 43-63.